A pulse check for trends in sea turtle numbers across the globe.

Population declines of vertebrates are common, but rebuilding marine life may be possible. We assessed trends in sea turtle numbers globally, building 61 time series of abundance extending beyond 2015, representing monitoring in >1200 years. Increases were widespread with significant upward trends, no significant change, and significant downward trends in 28, 28, and 5 time series, respectively. For example, annual nest numbers increased between 1980 and 2018 from around 4,000 to 16,000 for green turtles at Aldabra (Seychelles, Indian Ocean) and between 2008 and 2020 from around 500 to 35,000 for loggerhead turtles in Sal (Cape Verde, north Atlantic). However, conservation concerns remain. Major populations may experience declines, such as loggerhead turtles in Oman, while previous upward trends can be reversed, as with green turtles nesting at Tortuguero (Costa Rica, Caribbean). Further, decreases in abundance were evident in several leatherback turtle time series. These concerns show there is no room for complacency for sea turtle conservation.

Thermal vulnerability of sea turtle foraging grounds around the globe.

Anticipating and mitigating the impacts of climate change on biodiversity requires a comprehensive understanding on key habitats utilized by species. Yet, such information for high mobile marine megafauna species remains limited. Here, we compile a global database comprising published satellite tracking data (n = 1035 individuals) to spatially delineate foraging grounds for seven sea turtle species and assess their thermal stability. We identified 133 foraging areas distributed around the globe, of which only 2% of the total surface is enclosed within an existing protected area. One-third of the total coverage of foraging hotspots is situated in high seas, where conservation focus is often neglected. Our analyses revealed that more than two-thirds of these vital marine habitats will experience new sea surface temperature (SST) conditions by 2100, exposing sea turtles to potential thermal risks. Our findings underline the importance of global ocean conservation efforts, which can meet climate challenges even in remote environments.

Pigmented Squamous Cell Carcinoma In Situ of the Eyelid.

This case report describes a diagnosis of pigmented squamous cell carcinoma in situ in a female patient aged 61 years who presented with a pigmented lesion on her medial canthus that had been growing over a 2-year period.

Tendon-Sparing Extraocular Muscle Enlargement Associated With Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory, sensorimotor polyneuropathy. It has presented with a variety of orbital and neuro-ophthalmic manifestations, including cranial nerve hypertrophy and a single case of extraocular muscle enlargement. The authors present a second case of tendon-sparing, extraocular muscle enlargement, resulting in new-onset diplopia and strabismus in a teenager with CIDP. The workup ruled out alternative causes of extraocular muscle enlargement, such as hyperthyroidism, inflammation, or malignancy. As with other cases of CIDP, management involved a combination of immunoglobulin therapy and anti-inflammatory medications. The patient experienced resolution of his symptoms, and radiologic improvement was noted in the muscle enlargement. As many CIDP patients have a favorable treatment response and long-term prognosis, awareness of this rare disease with an early and accurate diagnosis is important.

Physiologically engineered porous titanium/brushite scaffolds for critical-size bone defects: A design and manufacturing study.

Repairing critical-size bone defects still represents a critical clinical challenge in the field of trauma surgery. This study focuses on a physiological design and manufacturing of porous composite scaffold (titanium Ti with 10 % mole iron doped brushite DCPD-Fe3+) which can mimic the biomechanical properties of natural cortical bone, specifically for the purpose of repairing critical-size defects. To achieve this, the principle of design of experiments (DOE) was applied for investigating the impact of sintering temperature, mineral ratio, and volume fraction of porosity on the mechanical properties of the fabricated scaffolds. The fabricated scaffolds had open porosity up to 60 %, with pore size approximately between 100 µm and 850 µm. The stiffness of the porous composite scaffolds varied between 3.30 GPa and 20.50 GPa, while the compressive strength ranged from approximately 130 MPa-165 MPa at sintering temperatures equal to or exceeding 1000 °C. Scaffolds with higher porosity and mineral content demonstrated lower stiffness values, resembling natural bone. Numerical simulation was employed by Ansys Workbench to investigate the stress and strain distribution of a critical size defect in mid-shaft femur which was designed to be replaced with the fabricated scaffold. The fabricated scaffolds showed flexible biomechanical behaviour at the bone/scaffold interface, generating lower stress levels and indicating a better match with the femoral shaft stiffness. The experimental and numerical findings demonstrated promising applications for manufacturing a patient-specific bone scaffold for critical and potentially large defects for reducing stress shielding and minimizing non-union risk.

Development of a novel apigenin prodrug programmed for alkaline-phosphatase instructed self-inhibition to combat cancer.

Elevated levels of alkaline phosphatase (ALP) in the tumor microenvironment (TME) are a hallmark of cancer progression and thus inhibition of ALP could serve as an effective approach against cancer. Herein, we developed a novel prodrug approach to tackle cancer that bears self-inhibiting alkaline phosphatase-responsiveness properties that can enhance at the same time the solubility of the parent compound. To probe this novel concept, we selected apigenin as the cytotoxic agent since we first unveiled, that it directly interacts and inhibits ALP activity. Consequently, we rationally designed and synthesized, using a self-immolative linker, an ALP responsive apigenin-based phosphate prodrug, phospho-apigenin. Phospho-apigenin markedly increased the stability of the parent compound apigenin. Furthermore, the prodrug exhibited enhanced antiproliferative effect in malignant cells with elevated ALP levels, compared to apigenin. This recorded potency of the developed prodrug was further confirmed in vivo where phospho-apigenin significantly suppressed by 52.8% the growth of PC-3 xenograft tumors.Communicated by Ramaswamy H. Sarma.

Priorities for Mediterranean marine turtle conservation and management in the face of climate change.

As climate-related impacts threaten marine biodiversity globally, it is important to adjust conservation efforts to mitigate the effects of climate change. Translating scientific knowledge into practical management, however, is often complicated due to resource, economic and policy constraints, generating a knowledge-action gap. To develop potential solutions for marine turtle conservation, we explored the perceptions of key actors across 18 countries in the Mediterranean. These actors evaluated their perceived relative importance of 19 adaptation and mitigation measures that could safeguard marine turtles from climate change. Of importance, despite differences in expertise, experience and focal country, the perceptions of researchers and management practitioners largely converged with respect to prioritizing adaptation and mitigation measures. Climate change was considered to have the greatest impacts on offspring sex ratios and suitable nesting sites. The most viable adaptation/mitigation measures were considered to be reducing other pressures that act in parallel to climate change. Ecological effectiveness represented a key determinant for implementing proposed measures, followed by practical applicability, financial cost, and societal cost. This convergence in opinions across actors likely reflects long-standing initiatives in the Mediterranean region towards supporting knowledge exchange in marine turtle conservation. Our results provide important guidance on how to prioritize measures that incorporate climate change in decision-making processes related to the current and future management and protection of marine turtles at the ocean-basin scale, and could be used to guide decisions in other regions globally. Importantly, this study demonstrates a successful example of how interactive processes can be used to fill the knowledge-action gap between research and management.

Composite PLGA-Nanobioceramic Coating on Moxifloxacin-Loaded Akermanite 3D Porous Scaffolds for Bone Tissue Regeneration.

Silica-based ceramics doped with calcium and magnesium have been proposed as suitable materials for scaffold fabrication. Akermanite (Ca2MgSi2O7) has attracted interest for bone regeneration due to its controllable biodegradation rate, improved mechanical properties, and high apatite-forming ability. Despite the profound advantages, ceramic scaffolds provide weak fracture resistance. The use of synthetic biopolymers such as poly(lactic-co-glycolic acid) (PLGA) as coating materials improves the mechanical performance of ceramic scaffolds and tailors their degradation rate. Moxifloxacin (MOX) is an antibiotic with antimicrobial activity against numerous aerobic and anaerobic bacteria. In this study, silica-based nanoparticles (NPs) enriched with calcium and magnesium, as well as copper and strontium ions that induce angiogenesis and osteogenesis, respectively, were incorporated into the PLGA coating. The aim was to produce composite akermanite/PLGA/NPs/MOX-loaded scaffolds through the foam replica technique combined with the sol-gel method to improve the overall effectiveness towards bone regeneration. The structural and physicochemical characterizations were evaluated. Their mechanical properties, apatite forming ability, degradation, pharmacokinetics, and hemocompatibility were also investigated. The addition of NPs improved the compressive strength, hemocompatibility, and in vitro degradation of the composite scaffolds, resulting in them keeping a 3D porous structure and a more prolonged release profile of MOX that makes them promising for bone regeneration applications.

Development of a Novel Apigenin Dosage form as a Substitute for the Modern Triple Antithrombotic Regimen.

The simultaneous administration of three antiplatelet agents has been proposed as an efficient strategy for the secondary prevention of atherothrombotic events and is included in the European guidelines. However, this strategy presented an increased risk of bleeding; therefore, the identification of new antiplatelet agents, with improved efficacy and diminished side effects, is of great importance. In silico studies, UPLC/MS Q-TOF plasma stability, in vitro platelet aggregation experiments, and pharmacokinetic studies were exploited. In the present study, it has been predicted that the flavonoid apigenin could target different platelet activation pathways, including P2Y12, protease-activated receptor-1 (PAR-1), and cyclooxygenase 1 (COX-1). To enhance apigenin's potency, hybridization with docosahexaenoic acid (DHA) was performed, as fatty acids have illustrated potent efficacy against cardiovascular diseases (CVDs). The new molecular hybrid, termed 4'-DHA-apigenin, demonstrated enhanced inhibitory activity against platelet aggregation induced by thrombin receptor activator peptide-6 (TRAP-6), adenosine diphosphate (ADP), and arachidonic acid (AA), with respect to the parent apigenin. The 4'-DHA-apigenin hybrid illustrated an almost 2-fold enhanced inhibitory activity, with respect to apigenin, and an almost 3-fold enhanced inhibitory activity, with respect to DHA, for the ADP-induced platelet aggregation. Additionally, the hybrid presented a more than 12-fold enhanced inhibitory activity with respect to DHA for the TRAP-6 induced platelet aggregation. Furthermore, a 2-fold enhanced inhibitory activity was recorded for the 4'-DHA-apigenin hybrid for the AA-induced platelet aggregation with respect to apigenin. To surmount the reduced LC-MS based plasma stability, a novel dosage form in olive oil has been developed. The 4'-DHA-apigenin olive oil-based formulation presented an enhanced antiplatelet inhibitory effect in three activation pathways. To further explore the pharmacokinetic profile of 4'-DHA-apigenin in olive oil formulations, a UPLC/MS Q-TOF protocol has been established to quantify the serum levels of apigenin after oral administration to C57BL/6J wild type mice. The olive oil-based formulation of 4'-DHA-apigenin demonstrated an increase in apigenin bioavailability of 262 %. This study may offer a new therapeutic strategy tailored to improve the treatment of CVDs.

Synthesis and Study of Fully Biodegradable Composites Based on Poly(butylene succinate) and Biochar.

Biodegradable polymers offer a promising alternative to the global plastic problems and especially in the last decade, to the microplastics problems. For the first time, samples of poly(butylene succinate) (PBSu) biocomposites containing 1, 2.5, and 5 wt% biochar (BC) were prepared by in situ polymerization via the two-stage melt polycondensation procedure. BC was used as a filler for the PBSu to improve its mechanical properties, thermal transitions, and biodegradability. The structure of the synthesized polymers was examined by 1H and 13C nuclear magnetic resonance (NMR) and X-Ray diffraction (XRD) along with an estimation of the molecular weights, while differential scanning calorimetry (DSC) and light flash analysis (LFA) were also employed to record the thermal transitions and evaluate the thermal conductivity, respectively. It was found that the amount of BC does not affect the molecular weight of PBSu biocomposites. The fine dispersion of BC, as well as the increase in BC content in the polymeric matrix, significantly improves the tensile and impact strengths. The DSC analysis results showed that BC facilitates the crystallization of PBSu biocomposites. Due to the latter, a mild and systematic increase in thermal diffusivity and conductivity was recorded indicating that BC is a conductive material. The molecular mobility of PBSu, local and segmental, does not change significantly in the biocomposites, whereas the BC seems to cause an increase in the overall dielectric permittivity. Finally, it was found that the enzymatic hydrolysis degradation rate of biocomposites increased with the increasing BC content.

Synthesis and Testing of Analogs of the Tuberculosis Drug Candidate SQ109 against Bacteria and Protozoa: Identification of Lead Compounds against Mycobacterium abscessus and Malaria Parasites.

SQ109 is a tuberculosis drug candidate that has high potency against Mycobacterium tuberculosis and is thought to function at least in part by blocking cell wall biosynthesis by inhibiting the MmpL3 transporter. It also has activity against bacteria and protozoan parasites that lack MmpL3, where it can act as an uncoupler, targeting lipid membranes and Ca2+ homeostasis. Here, we synthesized 18 analogs of SQ109 and tested them against M. smegmatis, M. tuberculosis, M. abscessus, Bacillus subtilis, and Escherichia coli, as well as against the protozoan parasites Trypanosoma brucei, T. cruzi, Leishmania donovani, L. mexicana, and Plasmodium falciparum. Activity against the mycobacteria was generally less than with SQ109 and was reduced by increasing the size of the alkyl adduct, but two analogs were ∼4-8-fold more active than SQ109 against M. abscessus, including a highly drug-resistant strain harboring an A309P mutation in MmpL3. There was also better activity than found with SQ109 with other bacteria and protozoa. Of particular interest, we found that the adamantyl C-2 ethyl, butyl, phenyl, and benzyl analogs had 4-10× increased activity against P. falciparum asexual blood stages, together with low toxicity to a human HepG2 cell line, making them of interest as new antimalarial drug leads. We also used surface plasmon resonance to investigate the binding of inhibitors to MmpL3 and differential scanning calorimetry to investigate binding to lipid membranes. There was no correlation between MmpL3 binding and M. tuberculosis or M. smegmatis cell activity, suggesting that MmpL3 is not a major target in mycobacteria. However, some of the more active species decreased lipid phase transition temperatures, indicating increased accumulation in membranes, which is expected to lead to enhanced uncoupler activity.

Are Mediterranean marine threatened species at high risk by climate change?

Rapid anthropogenic climate change is driving threatened biodiversity one step closer to extinction. Effects on native biodiversity are determined by an interplay between species' exposure to climate change and their specific ecological and life-history characteristics that render them even more susceptible. Impacts on biodiversity have already been reported, however, a systematic risk evaluation of threatened marine populations is lacking. Here, we employ a trait-based approach to assess the risk of 90 threatened marine Mediterranean species to climate change, combining species' exposure to increased sea temperature and intrinsic vulnerability. One-quarter of the threatened marine biodiversity of the Mediterranean Sea is predicted to be under elevated levels of climate risk, with various traits identified as key vulnerability traits. High-risk taxa including sea turtles, marine mammals, Anthozoa and Chondrichthyes are highlighted. Climate risk, vulnerability and exposure hotspots are distributed along the Western Mediterranean, Alboran, Aegean, and Adriatic Seas. At each Mediterranean marine ecoregion, 21%-31% of their threatened species have high climate risk. All Mediterranean marine protected areas host threatened species with high risk to climate change, with 90% having a minimum of 4 up to 19 species of high climate risk, making the objective of a climate-smart conservation strategy a crucial task for immediate planning and action. Our findings aspire to offer new insights for systematic, spatially strategic planning and prioritization of vulnerable marine life in the face of accelerating climate change.

Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis.

Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically, PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO, and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system (CNS)-multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.

Severe Gastritis Due to Nivolumab Treatment of a Metastatic Melanoma Patient.

Nivolumab, an anti-PD-1 check point inhibitor, is an immunotherapeutic agent, representing a major step in the treatment of melanoma. However, its use is associated with severe toxicities. Among them, gastrointestinal (GI) disorders from the lower GI tract have been widely reported. On the contrary, disorders from the upper GI tract are rare. Such a case of delayed nivolumab induced severe gastritis in a 53-year-old Caucasian female patient suffering metastatic melanoma is described. The patient's symptoms from the upper GI tract began 4 months after nivolumab treatment initiation. The diagnosis was based on imaging, including PET/CT, endoscopical and pathological findings. The side effect was successfully treated with prolonged administration of proton pump inhibitors and corticosteroids. There are only a few cases of immune check point inhibitors (ICPis) induced upper GI tract disorders, while it seems that the symptoms from nivolumab induced upper GI tract damages appear later than those reported in the lower part. Nivolumab, among other side effects, may cause severe gastritis. Hence, this pathological entity should be included in the list of this drug's side effects.

A catastrophic change in a european protected wetland: From harmful phytoplankton blooms to fish and bird kill.

Understanding the processes that underlay an ecological disaster represents a major scientific challenge. Here, we investigated phytoplankton and zooplankton community changes before and during a fauna mass kill in a European protected wetland. Evidence on gradual development and collapse of harmful phytoplankton blooms, allowed us to delineate the biotic and abiotic interactions that led to this ecological disaster. Before the mass fauna kill, mixed blooms of known harmful cyanobacteria and the killer alga Prymnesium parvum altered biomass flow and minimized zooplankton resource use efficiency. These blooms collapsed under high nutrient concentrations and inhibitory ammonia levels, with low phytoplankton biomass leading to a dramatic drop in photosynthetic oxygenation and a shift to a heterotrophic ecosystem phase. Along with the phytoplankton collapse, extremely high numbers of red planktonic crustaceans-Daphnia magna, visible through satellite images, indicated low oxygen conditions as well as a decrease or absence of fish predation pressure. Our findings provide clear evidence that the mass episode of fish and birds kill resulted through severe changes in phytoplankton and zooplankton dynamics, and the alternation on key abiotic conditions. Our study highlights that plankton-related ecosystem functions mirror the accumulated heavy anthropogenic impacts on freshwaters and could reflect a failure in conservation and restoration measures.

Functional extinction of dugongs in China.

Dugongs (Dugong dugon) experienced a serious population decline in China during the twentieth century, and their regional status is poorly understood. To determine their current distribution and status, we conducted a large-scale interview survey of marine resource users across four Chinese provinces and reviewed all available historical data covering the past distribution of dugongs in Chinese waters. Only 5% of 788 respondents reported past dugong sightings, with a mean last-sighting date of 23 years earlier, and only three respondents reported sightings from within the past 5 years. Historical records of dugongs peak around 1960 and then decrease rapidly from 1975 onwards; no records are documented after 2008, with no verified field observations after 2000. Based on these findings, we are forced to conclude that dugongs have experienced rapid population collapse during recent decades and are now functionally extinct in China. Our study provides evidence of a new regional loss of a charismatic marine megafaunal species, and the first reported functional extinction of a large vertebrate in Chinese marine waters. This rapid documented population collapse also serves as a sobering reminder that extinctions can occur before effective conservation actions are developed.

4D marine conservation networks: Combining 3D prioritization of present and future biodiversity with climatic refugia.

Given the accelerating rate of biodiversity loss, the need to prioritize marine areas for protection represents a major conservation challenge. The three-dimensionality of marine life and ecosystems is an inherent element of complexity for setting spatial conservation plans. Yet, the confidence of any recommendation largely depends on shifting climate, which triggers a global redistribution of biodiversity, suggesting the inclusion of time as a fourth dimension. Here, we developed a depth-specific prioritization analysis to inform the design of protected areas, further including metrics of climate-driven changes in the ocean. Climate change was captured in this analysis by considering the projected future distribution of >2000 benthic and pelagic species inhabiting the Mediterranean Sea, combined with climatic stability and heterogeneity metrics of the seascape. We identified important areas based on both biological and climatic criteria, where conservation focus should be given in priority when designing a three-dimensional, climate-smart protected area network. We detected spatially concise, conservation priority areas, distributed around the basin, that protected marine areas almost equally across all depth zones. Our approach highlights the importance of deep sea zones as priority areas to meet conservation targets for future marine biodiversity, while suggesting that spatial prioritization schemes, that focus on a static two-dimensional distribution of biodiversity data, might fail to englobe both the vertical properties of species distributions and the fine and larger-scale impacts associated with climate change.

Exploration of Betalains and Determination of the Antioxidant and Cytotoxicity Profile of Orange and Purple Opuntia spp. Cultivars in Greece.

Replacing synthetic dyes with natural pigments has gained great attention over the past years in the food industry, due to the increased alertness of consumers for nontoxic and natural additives. Betalains are water-soluble nitrogenous natural pigments that are used as natural colorants in food industries, due to their applicability and their rich pharmacological profile including antioxidant, antimicrobial, and anticancer properties. Therefore, there is a need for a detailed exploration of betalains to fully exploit their properties. Opuntia spp. plants are one of the primary sources of betalains. The objective of this study was to identify betalain phytochemical content in prickly pear cactus of two different Opuntia species from Greece (an Opuntia ficus-indica (L.) Mill (OFI) orange prickly pear cultivar and an Opuntia spp. purple prickly pear cultivar) using modern analytical techniques as also to evaluate their antioxidant and cytotoxicity profile. To achieve this we used an array of analytical techniques, including ultra-violet-vis (UV-Vis) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and liquid chromatography-high resolution mass spectrometry (LC-HRMS) as also cell based in vitro assays. These enabled us to establish a rapid approach that can distinguish the different Opuntia spp. cultivars based on their phytochemical constituents through untargeted metabolomics analysis using ultra-high performance liquid chromatography-mass spectrometry - quadrupole time-of-flight (UPLC/MS Q-TOF). These findings could allow a further exploitation of Opuntia species and especially their enriched betalain phytochemical profile as viable source of natural food colorants.

Novel climates in European river sub-basins pose a challenge for the persistence of freshwater fish.

Understanding how climate change would affect biota inhabiting sensitive and highly valuable ecosystems, spanning broad regions, is essential to anticipate implications for biodiversity and humans, and to identify management and mitigation measures. Traditionally, assessments to evaluate climatic risks over broad regions and for many species implement models that allow the projection of a climate-driven redistribution of biodiversity. Still, the wealth and quality of the background information (e.g., species presence data) constrain the accuracy and representativeness of such frameworks. As an alternative, here, we developed a twofold approach to assess the vulnerability of 86 European freshwater fish. We accounted for shifts in a multidimensional climatic space of broader hydrological units that host freshwater bodies in Europe. We then linked metrics of their climatic stability with groups of species, which were generated from six intrinsic traits that shape species adaptive capacity to climate change. Our results demonstrated that the climate of all (n = 538) river sub-basins hosted in the European Union territory would change by 2100, with more than 10% of them being projected to gain completely novel climates. Sub-basins predicted to lose more than 90% of their current climatic space were mainly identified in the area around the Baltic Sea, but also in Mediterranean regions (i.e., Iberian Peninsula). Important numbers of fish species with life history strategies that are considered susceptible to climate change were identified in sub-basins that were predicted to completely lose their current climatic conditions. Clearly, the climate of valuable freshwater ecosystems is changing, affecting species and their communities in varying ways. The risk is high, and is not limited to specific regions; thus, new effective strategies and measures are needed to conserve freshwater fish and their habitats across Europe.

Spatial heterogeneity and temporal stability characterize future climatic refugia in Mediterranean Europe.

Climate plays a major role in shaping biodiversity patterns over time and space, with ongoing changes leading to the reorganization of ecosystems, which challenges conservation initiatives. Identifying areas that could serve as possible climate change refugia for future biodiversity is, thus, critical for both conservation and management. Here, we identify potential future climatic refugia within the Euro-Mediterranean biome, which is a global biodiversity hotspot, while accounting for multiple emission climate change projections over the next 50 years. We developed two metrics of climatic variability: temporal stability and spatial heterogeneity. We then used a systematic conservation planning approach to identify climate-based priority areas. While we used a climate-based, species-neutral methodology, we deliberately implemented low climatic velocity thresholds, so that the identified climatic refugia would even be compatible with the needs of species with low dispersal capacity, such as plants. Our projections showed that future climatic refugia would be more frequently observed in mid-altitudes, for gradients with steep elevations, and mainly in the eastern part of the Euro-Mediterranean biome, with possible conflicts with existing land uses and future conservation implications. Climatic, land use, and topography results indicated that only a limited number of refugia would be hosted by high elevation habitats (>1500 m), raising possible concerns about the biodiversity of Mediterranean mountain regions. Our analyses show that the current network of protected areas captures future climatic refugia disproportionally, despite their importance for safeguarding present and future biodiversity in the Mediterranean. Key climatic refugia could limit the impacts of future climate change on biodiversity in mid-altitude and mountainous regions, and should be included in management guidelines for a climate-ready conservation design in the Mediterranean biome.